Narrowing and occlusion of the coronary arteries constitute one of the major causes of heart disease. Coronary artery disease leads to perfusion defects which in turn lead to myocardial infarction.
Currently, the only reliable method for the detection of myocardial perfusion abnormalities is nuclear imaging. However, this imaging technique is relatively expensive and takes several hours to complete. By far the most widely used imaging method in cardiac examination is ultrasonography. However, at present, it is not possible to determine myocardial perfusion abnormalities with this imaging method.
The evaluation of myocardial perfusion is particularly important before and after interventional procedures. The determination of the restoration of myocardial blood flow after intervention is a critical factor in confirming the success of this procedure.
Various echo contrast agents are currently in clinical development. However, these agents provide only transient images of myocardial perfusion and they suffer from problems such as attenuation. The perfusion images generated are of insufficient duration to allow the clinician to generate accurate 3-D reconstructions.
A further disadvantage of existing intravenous (IV) agents is that myocardial perfusion images require the use of harmonic, triggered imaging techniques. At present, few suitable machines are available. Further, triggered images fail to generate real time images. Therefore, it is not possible to generate moving images of the myocardium whilst visualising echocontrast.
Ultrasound contrast agents can be introduced into the body to reflect or absorb ultrasound energy, or to resonate when exposed to such energy, and thereby provide an enhanced image of a part of the body. Examples of such contrast agents, in the form of hollow microcapsules, are given in WO-A-92/18164, WO-A-94/08627 and WO-A-96/15814. Such agents are injected into the patient's bloodstream and then the patient is subjected to ultrasound radiation.